Most cited article - PubMed ID 33557282
Human Uterus Transplantation from Living and Deceased Donors: The Interim Results of the First 10 Cases of the Czech Trial
Uterus transplantation is the surgical treatment for absolute uterine factor infertility (AUFI), a congenital or acquired condition characterized by the absence of a uterus. More than 80 transplants have been performed worldwide, resulting in more than 30 live births, originating both from living and deceased donors. The collection of published articles on deceased donor uterus transplantations was performed in PubMed and SCOPUS by searching for the terms "Uterus transplantation" AND "deceased donor"; from the 107 articles obtained, only case reports and systematic reviews of deceased donor uterus transplantations and the resulting live births were considered for the present manuscript. The extracted data included the date of surgery (year), country, recipient (age and cause of AUFI) and donor (age and parity) details, outcome of recipient surgery (hysterectomy), and live births (date and gestational age). The search of peer-reviewed publications showed 24 deceased donor uterus transplantations and 12 live births (a birth rate of 66%) with a 25% occurrence of graft loss during follow-up (6 of 24). Among this series, twelve transplants were performed in the USA (seven births), five in the Czech Republic (one birth), three in Italy (one birth), two in Turkey (two births), and two in Brazil (one birth). The median recipient age was 29.8 years (range 21-36), while the median donor age was 36.1 years (range 20-57). Of 24 recipients, 100% were affected by MRKH (Mayer-Rokitanski-Kuster-Hauser) syndrome. Two live births were reported from nulliparous donors. Deceased donor uterus transplantation birth rates are very similar to the living donor rates reported in the literature, but ethical implications could be less important in the first group. It is necessary to register every case in the International Registry for Uterus Transplantation in order to perform a systematic review and comparison with living donor rates.
- Keywords
- AUFI, birth rate, deceased donor, living donor, uterus transplantation,
- MeSH
- Tissue Donors statistics & numerical data MeSH
- Adult MeSH
- Mullerian Ducts abnormalities surgery MeSH
- Humans MeSH
- Live Birth MeSH
- 46, XX Disorders of Sex Development surgery complications MeSH
- Pregnancy MeSH
- Uterus * transplantation abnormalities MeSH
- Congenital Abnormalities MeSH
- Infertility, Female surgery MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Geographicals
- Brazil MeSH
- Czech Republic MeSH
- Italy MeSH
- Turkey MeSH
BACKGROUND: Diagnosis of rejection after uterus transplantation is based on histopathological examination of ectocervical biopsies. Inflammation at the stromal-epithelial interface is the backbone of the histopathological classification proposed by our group in 2017. However, the reproducibility of this grading scheme has not been tested, and it is unclear whether it covers the full morphological spectrum of rejection. METHODS: We present a multicenter study in which 5 pathologists from 4 uterus transplantation centers performed 2 rounds of grading on 145 and 48 cervical biopsies, respectively. Three of the centers provided biopsies. Additionally, the presence of perivascular stromal inflammation was recorded. During discussions after the first round, further histological lesions (venous endothelial inflammation and apoptosis) were identified for closer evaluation and added to the panel of lesions to score in the second round. All participants completed a questionnaire to explore current practices in handling and reporting uterus transplant biopsies. RESULTS: Cervical biopsies were commonly performed in all centers to monitor rejection. Intraobserver reproducibility of rejection grading (performed by 1 rater) was excellent, whereas interobserver reproducibility was moderate and did not improve in the second round. Reproducibility of perivascular stromal inflammation was moderate but unsatisfactory for venous endothelial inflammation and apoptosis. All lesions were more frequent in, but not restricted to, biopsies with rejection patterns. CONCLUSIONS: Grading of rejection in cervical biopsies is reproducible and applicable to biopsies from different centers. Diagnosis of rejection may be improved by adding further histological lesions to the grading system; however, lesions require rigorous consensus definition.
- Publication type
- Journal Article MeSH
Arterial blood to the human uterus is provided by a pair of uterine arteries (UA) and supported by terminal branches of ovarian (OA) and vaginal arteries (VA). Literature reports the existence of ipsilateral and contralateral anastomoses between these arteries and the UA, but data on the prevalence of such anastomoses are discrepant. The aim of this trial is to study whether contralateral and ipsilateral anastomoses exist. We studied nine human uterine specimens, which were obtained from (i) human cadavers (n = 6), (ii) uterine transplant recipients (n = 2), and (iii) one altruistic uterine donor (n = 1). We injected India ink into the graft through the UA of each specimen (n = 8) or OA (n = 1). We semiquantitatively observed and evaluated the extent of the injection on horizontal, vertical, and transmural levels. The dye permeated beyond the midline in 9/9 (100 %) cases. Near-complete/complete permeation to the contralateral side was observed in 6/9 (66 %) cases. The dye permeated ipsilaterally throughout all uterine levels in 8/8 cases (100 %) of UA injection. The entire wall of the myometrium was permeated in 2/9 (22 %) cases. In 7/9 (78 %) cases, the wall of the myometrium was permeated less than halfway through. In conclusion, the preliminary results of this study prove the existence of ipsilateral and contralateral anastomoses. Complete transmural injection was observed in only 22 % of cases; however, this finding does not provide information about the functional capacity of these anastomoses. More data and studies are necessary to make definitive conclusions.
Uterus transplantation (UTx) is a promising treatment option for women who wish to give birth but suffer from absolute uterine factor infertility. This paper presents an interim analysis of a trial focusing on the causes, prevention, diagnosis, and management of graft thrombosis. Our team analyzed 10 cases of UTx (recipients numbered 1 to 10). Early thrombosis developed in 2 of 10 (20 %) recipients, and thrombectomy and temporary viability preservation were achieved in both cases. However, re-thrombosis developed in both cases, and a graft hysterectomy was carried out. In recipient number 2, vascular changes might have contributed to graft thrombosis. The histopathological finding of the explant revealed subintimal excentric fibrosis with focal sclerotic changes. In recipient number 8, thrombosis was facilitated by external compression of the vascular pedicles by the hematoma as well as production of de novo donor-specific antibodies. Thrombosis led to graft loss in both cases despite an attempt at a thrombectomy. Therefore, the focus must be on prevention including a thorough evaluation of the donor candidate. In the postoperative course, perfusion is closely followed-up with an ultrasound, Doppler flow monitoring, and macroscopic evaluation of the cervix. In the event that findings are unclear, a relaparotomy should be promptly indicated. If thrombosis is revealed, a thrombectomy and an attempt to salvage the graft are indicated; however, the role of this strategy is questionable due to the low chance of long-term success. The indication of upfront graft removal and early re-transplantation in the treatment of uterine graft remains debatable.
- MeSH
- Tissue Donors MeSH
- Fibrosis MeSH
- Humans MeSH
- Transplants * MeSH
- Thrombosis * etiology prevention & control MeSH
- Uterus transplantation MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
